What Is the Significance of the Serotonin Uptake Inhibition and the CYP Enzyme Inhibition?
The greater degree of serotonin uptake inhibition that occurred in this patient as a result of the increased accumulation of fluoxetine increased the likelihood that she would experience at least a mild variant of the serotonin syndrome. For the same reason, she would have experienced more aggravation of her Parkinsonian symptoms since serotonin has an inhibitory effect on dopamine cell firing in the brainstem.9 Thus, fluoxetine, like any SRI, would have pharmacodynamically interacted with haloperidol to antagonize dopamine function in her basal ganglia. In addition, by inhibition of CYP 3A3/4, fluoxetine may have modestly increased the haloperidol accumulation, resulting in a greater degree of dopamine blockade in her basal ganglia. Thus, this patient likely had combined pharmacodynamic and pharmacokinetic interactions between fluoxetine and haloperidol which in turn aggravated the haloperidol-Parkinson’s disease interaction we discussed initially. The interaction between fluoxetine a
